Trametinib thwarts activation of survival pathways induced by pro-ferroptotic drug conjugate ACXT-3102 resulting in enhanced pancreatic cancer cell death. (PubMed, Mol Cancer Ther) - Jul 3, 2025 - "Our group has developed a cancer-specific drug conjugate (ACXT-3102), consisting of a pro-apoptotic sigma-2 ligand as a delivery moiety (SV119), linked to an inhibitor of the cystine antiporter xCT (dm-Erastin), an established inducer of ferroptosis. We suspected this was a compensatory reaction and that ACXT-3102-induced cancer cell death would be augmented by inhibition of MAPK/ERK signaling. We successfully combined ACXT-3102 with trametinib (MEK inhibitor) to enhance the overall efficacy of treatment in vitro and in vivo, presumably by targeting ACXT-3102-induced upregulation of MAPK/ERK."
Journal • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • CASP3 • CASP7 • DUSP6 • GPX4
|
|
Brian A Van Tine; Dirk Spitzer; Kenneth F Newcomer; Kumar S Bishnupuri; Lauren Ross; Li Ye; Qingqing Gong; Rony Takchi; Suwanna Vangveravong; William G Hawkins
|